Trial Outcomes & Findings for Study of Oral ALXN1840 at 2 Dose Strengths in Healthy Adults (NCT NCT05303324)

Last Updated: 2023-08-02

Results Overview

The pharmacokinetic (PK) data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via inductively coupled plasma-mass spectroscopy (ICP-MS).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

Up to 240 hours postdose

Results posted on

2023-08-02

Participant Flow

Participants were randomized to 1 of 2 treatment sequences (A-B) or (B-A) in a crossover study design during 2 dosing periods. Participants were scheduled to receive either treatment A or B on Day 1 of each dosing period. There was a washout of at least 14 days between the dosing periods.

Participant milestones

Participant milestones
Measure	ALXN1840 Treatment Sequence A-B Period 1: Participants received ALXN1840 reference formulation administered orally as 1 enteric-coated (EC) tablet at 15 milligrams (mg) on Day 1 (Treatment A). Period 2: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B). There was a washout of at least 14 days between the dosing periods.	ALXN1840 Treatment Sequence B-A Period 1: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B). Period 2: Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1 (Treatment A). There was a washout of at least 14 days between the dosing periods.
Treatment Period 1 STARTED	25	23
Treatment Period 1 Received at Least 1 Dose of Study Drug	25	23
Treatment Period 1 COMPLETED	25	23
Treatment Period 1 NOT COMPLETED	0	0
Treatment Period 2 STARTED	25	23
Treatment Period 2 Received at Least 1 Dose of Study Drug	25	23
Treatment Period 2 COMPLETED	25	23
Treatment Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Oral ALXN1840 at 2 Dose Strengths in Healthy Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ALXN1840 Treatment Sequence A-B n=25 Participants Period 1: Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1 (Treatment A). Period 2: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B). There was a washout of at least 14 days between the dosing periods.	ALXN1840 Treatment Sequence B-A n=23 Participants Period 1: Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1 (Treatment B). Period 2: Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1 (Treatment A). There was a washout of at least 14 days between the dosing periods.	Total n=48 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	23 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	28.7 years STANDARD_DEVIATION 6.63 • n=5 Participants	28.1 years STANDARD_DEVIATION 6.04 • n=7 Participants	28.4 years STANDARD_DEVIATION 6.29 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 240 hours postdose

Population: The Pharmacokinetic Population included all participants who had sufficient plasma samples to enable the calculation of PK parameters of at least the area under the plasma concentration versus time curve (AUC) for at least 1 Treatment Period. Participants were grouped by period for each treatment for this analysis.

Outcome measures

Outcome measures
Measure	ALXN1840 Treatment A n=48 Participants Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	ALXN1840 Treatment B n=48 Participants Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.	Period 2: ALXN1840 Treatment A Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	Period 2: ALXN1840 Treatment B Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.
Maximum Observed (Plasma) Concentration (Cmax) of Total Molybdenum	173.10 nanograms (ng)/milliliter (mL) Standard Deviation 78.098	174.27 nanograms (ng)/milliliter (mL) Standard Deviation 62.956	—	—

PRIMARY outcome

Timeframe: Up to 240 hours postdose

Population: The Pharmacokinetic Population included all participants who had sufficient plasma samples to enable the calculation of PK parameters of at least the AUC for at least 1 Treatment Period. Participants were grouped by period for each treatment for this analysis.

The PK data of plasma total molybdenum were analyzed in the scope of this study as a surrogate measure for ALXN1840. Whole blood samples were collected for the measurement of plasma concentrations of total molybdenum via ICP-MS.

Outcome measures

Outcome measures
Measure	ALXN1840 Treatment A n=48 Participants Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	ALXN1840 Treatment B n=48 Participants Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.	Period 2: ALXN1840 Treatment A Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	Period 2: ALXN1840 Treatment B Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.
Area Under The Plasma Concentration Versus Time Curve From Time 0 (Dosing) to the Last Quantifiable Concentration (AUCt) of Total Molybdenum	7054.5 hours*ng/mL Standard Deviation 3634.92	6990.5 hours*ng/mL Standard Deviation 3020.70	—	—

SECONDARY outcome

Timeframe: Baseline up to Day 43

Population: The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.

An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAE was an AE that started during or after the first dose, or started prior to the first dose and increased in severity after the first dose. A related TEAE was defined as having a reasonable possibility the study intervention caused the AE as assessed by the investigator. Serious AEs (SAEs) were defined as any untoward medical occurrence that met at least 1 of the following serious criteria: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, other medically important serious event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Outcome measures

Outcome measures
Measure	ALXN1840 Treatment A n=25 Participants Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	ALXN1840 Treatment B n=23 Participants Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.	Period 2: ALXN1840 Treatment A n=23 Participants Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	Period 2: ALXN1840 Treatment B n=25 Participants Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) Any TEAE	7 Participants	5 Participants	4 Participants	8 Participants
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) Any TEAE leading to death	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) Any related TEAE	4 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With a Treatment-Emergent Adverse Event (TEAEs) Any serious TEAE (SAE)	0 Participants	0 Participants	0 Participants	0 Participants

Adverse Events

Period 1: ALXN1840 Treatment A

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Period 1: ALXN1840 Treatment B

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Period 2: ALXN1840 Treatment A

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Period 2: ALXN1840 Treatment B

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: +1.855.752.2356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Period 1: ALXN1840 Treatment A n=25 participants at risk Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	Period 1: ALXN1840 Treatment B n=23 participants at risk Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.	Period 2: ALXN1840 Treatment A n=23 participants at risk Participants received ALXN1840 reference formulation administered orally as 1 EC tablet at 15 mg on Day 1.	Period 2: ALXN1840 Treatment B n=25 participants at risk Participants received ALXN1840 test formulation administered orally as 3 EC tablets at 5 mg (15 mg total) on Day 1.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Eye disorders Eye pruritus	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Gastrointestinal disorders Diarrhoea	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Gastrointestinal disorders Toothache	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
General disorders Catheter site pain	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
General disorders Medical device site reaction	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Infections and infestations Viral upper respiratory tract infection	8.0% 2/25 • Number of events 2 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Infections and infestations Upper respiratory tract infection	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Infections and infestations Viral infection	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Infections and infestations Candida infection	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Infections and infestations Viral labyrinthitis	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Musculoskeletal and connective tissue disorders Muscle twitching	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Nervous system disorders Dizziness	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	8.0% 2/25 • Number of events 2 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Nervous system disorders Presyncope	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Skin and subcutaneous tissue disorders Rash	8.0% 2/25 • Number of events 2 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Skin and subcutaneous tissue disorders Butterfly rash	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.3% 1/23 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/25 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	0.00% 0/23 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.	4.0% 1/25 • Number of events 1 • Baseline up to Day 43 The Safety Population included all participants who received at least 1 dose of study drug. Participants were analyzed as randomized.